NR4A3 Immunostain Is a Highly Sensitive and Specific Marker for Acinic Cell Carcinoma in Cytologic and Surgical Specimens.

TitleNR4A3 Immunostain Is a Highly Sensitive and Specific Marker for Acinic Cell Carcinoma in Cytologic and Surgical Specimens.
Publication TypeJournal Article
Year of Publication2021
AuthorsViswanathan K, Beg S, He B, Zhang T, Cantley R, Lubin DJ, Shi Q, Maleki Z, Asiry S, Rao R, Katabi N, Nakaguro M, Faquin WC, Sadow PM, Siddiqui MT, Scognamiglio T
JournalAm J Clin Pathol
Date Published2021 Sep 11
ISSN1943-7722
Abstract

OBJECTIVES: Salivary gland acinic cell carcinoma (AciCC) has recognizable cytomorphologic features that can overlap with benign and malignant entities, creating a diagnostic challenge. AciCC harbors a t(4;9) translocation increasing nuclear receptor subfamily 4 group A member 3 (NR4A3) expression, detectable by immunohistochemistry (IHC) on surgical resection (SR). NR4A3 IHC cytology data are limited. Here, we examine NR4A3 IHC on smears, cell blocks (CBs), and SRs of AciCC and its mimickers.

METHODS: Our cohort comprised AciCC (including high-grade transformation), secretory carcinoma, mucoepidermoid carcinoma (MEC), Warthin tumor, pleomorphic adenoma (PA), cellular PA, carcinoma ex-PA, oncocytic carcinoma, oncocytoma, and nodular oncocytosis. NR4A3 IHC (Santa Cruz Biotechnology and Origene antibodies) was positive if more than 5% tumor cells showed nuclear staining.

RESULTS: Among CBs, 90% of AciCC cases and none of the mimickers expressed NR4A3. Among SRs, 100% of AciCC cases showed diffuse NR4A3, whereas one high-grade MEC expressed focal NR4A3. Concordance was 95% with two antibody clones. Sensitivity, specificity, positive predictive value, and negative predictive value were 90%, 100%, 100%, and 94.7% for CBs and 100%, 98.8%, 92.3%, and 100% for SRs, respectively. NR4A3 immunostaining was demonstrable on smears from an AciCC case.

CONCLUSIONS: NR4A3 IHC can be a robust diagnostic tool to identify AciCC, especially for cytology specimens.

DOI10.1093/ajcp/aqab099
Alternate JournalAm J Clin Pathol
PubMed ID34508546
Grant List1PO1CA240239-01 / / National Cancer Institute of the National Institutes of Health /
Related Faculty: 
Momin Siddiqui, M.D. Theresa Scognamiglio, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700